Actions of the systemically active metabotropic glutamate antagonist MPEP on sensory responses of thalamic neurones

It is known that metabotropic glutamate receptors of the subtypes mGlu1 and mGlu5 participate in nociceptive processing in the thalamus, an area of pr ime importance in supra-spinal sensory processing. Antagonists of these rec eptors thus have potential as centrally-acting analgesics. We have investig ated whether intravenous administration of the novel mGlu5-receptor antagon ist 6methyl-2-(phenylethynyl)-pyridine (MPEP) is able to reduce nociceptive responses of thalamic neurones. Extracellular recordings were made from si ngle thalamic neurones of adult male Wistar rats anaesthetised with urethan e. MPEP (1 mg/kg) reduced neuronal responses to noxious thermal stimuli to a mean of 24 +/- 4% of control within 10 min, whereas saline injections had no significant effect. Partial recovery was seen within 30-45 min after in jection. Responses of neurones to non-noxious stimuli were not significantl y affected by MPEP administration. In addition, MPEP caused an increase in the power of the slow-wave component (<1 Hz) of the electroencephalogram (E EG), but had no significant effect on peak frequency of the EEG or on heart rate. These results confirm that nociceptive responses of thalamic neurone s are mediated in part by mGlu5 receptors. Furthermore, the effectiveness o f intravenous MPEP suggests that such antagonists may be useful as centrall y-acting analgesics. (C) 2001 Elsevier Science Ltd. All rights reserved.